During epithelial-to-mesenchymal transition (EMT), cells acquire mesenchymal properties, which are thought to contribute to cancer invasion and metastasis. EMT is initiated by several transcription factors; among these, Twist1 is considered to be the master regulator, but it is not well understood how the full EMT program is orchestrated. In their study in this issue, Annapoorni Rangarajan and colleagues (Rangarajan et al., 2018) investigate the role of AMP-activated protein kinase (AMPK) in regulating EMT, because there have been conflicting results regarding its involvement in the process. They first show that direct activation of AMPK with an allosteric activator is sufficient to induce EMT, including an increased migration and invasion potential, in several cancer cell lines. Interestingly, in cancer cells that have already undergone EMT to varying extents, activation of AMPK further promoted the process, whereas its depletion or inactivation reversed the cellular changes associated with EMT. Furthermore, as shown here, AMPK appears to be required for EMT induced by different stimuli, such as hypoxia, TGF-β stimulation and Ras activation. Mechanistically, the data presented here suggest that AMPK directly upregulates Twist1 and increases its nuclear localisation. Taken together, these results establish a direct role for AMPK in the execution of EMT and also point to a possible new strategic avenue to counteract cancer invasion and metastasis.